Abstract
The use of lopinavir/ritonavir (LPV/r) has been associated with alterations in serum lipid and glucose levels. This study was designed to investigate the effects of melatonin (MT) and alpha lipoic acid (ALA) on LPV/r-induced changes in serum levels of triglycerides (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), very low density lipoprotein cholesterol (VLDL-C) and glucose (GL) levels in male albino rats. Rats in group A1 (placebo control) and group A2 (solvent control) were orally treated with normal saline and 1% ethanol respectively. Groups B-F contained 15 rats each which were divided into 3 groups of 5 rats each. Rats in group B were orally treated with MT (10 mg kg-1/day), ALA (10 mg kg-1/day) and a combination of MT and ALA, accordingly. Rats in group C were orally treated with 22.9/5.71, 45.6/11.4 and 91.4/22.9 mg kg-1/day of LPV/r, accordingly. Rats in groups D-F were orally treated with MT (10 mg kg-1/ day), ALA (10 mg kg-1/day) and combined doses of ALA and MT before oral treatment with 22.9/5.71, 45.6/11.4 and 91.4/22.9 mg kg-1/day of LPV/r, accordingly. All rats were treated for 30 days and at the end of the drug treatment, the serum levels of lipid fractions and glucose were evaluated. Treatment with MT and ALA significantly (p<0.05) decreased baseline serum levels of TG, TC, VLDL-C, LDL-C and GL, but these parameters were significantly (p<0.05) increased in a dose-dependent manner in LPV/r-treated rats when compared to placebo control. Administration of MT and ALA prior to treatment with LPV/r significantly (p<0.05) decreased serum levels of TG, TC, VLDL-C, LDL-C and GL when compared to LPV/r-treated rats. However, decreases obtained in rats pretreated with combined doses of MT and ALA were significantly (p<0.05) different when compared to their individual doses. This study showed that MT and ALA can serve as remedies for LPV/r-induced alterations in serum lipid and glucose levels.
Highlights
Active antiretroviral therapy (HAART) involves a combination of three or four classes of antiretroviral drugs
Due to the regulatory effects of MT and alpha lipoic acid (ALA) on lipid and glucose metabolism, this study investigated the effects of pretreatments with MT and ALA on baseline and LPV/r-induced serum levels of TG, total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), very low density lipoprotein cholesterol (VLDL-C) and GL levels in male albino rats
Pronounced and significant (p
Summary
Active antiretroviral therapy (HAART) involves a combination of three or four classes of antiretroviral drugs. Among the classes of antiretroviral drugs, alterations in plasma lipids and glucose levels are frequent class-related adverse effect of protease inhibitors which could limit their uses, especially in patients with pre-existing cardiovascular risk. Higher and frequent incidence of alterations in plasma lipid and glucose levels may be common with the use of lopinavir/ ritonavir(LPV/r) (Eron et al, 2006; Hill et al, 2009). Studies have shown that alterations in plasma lipids with LPV/r therapy could be characterized primarily by two factors: elevated plasma triglycerides (TG), and decreased HDLcholesterol (HDL-C). Alterations in serum glucose (GL) and lipid levels could involve oxidative stress. Higher serum levels of malondialdehyde have been reported in subjects with hyperlipidemia (Minhajuddinet al., 2005)
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